Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma

• Published in: Blood Vol. 126; no. 11; pp. 1294 - 1301
• Main Authors: Stewart, A. Keith, Jacobus, Susanna, Fonseca, Rafael, Weiss, Matthias, Callander, Natalie S., Chanan-Khan, Asher A., Rajkumar, S. Vincent
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.09.2015; American Society of Hematology
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Clinical Trials and Observations; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Lenalidomide; Male; Melphalan - administration & dosage; Middle Aged; Multiple Myeloma - drug therapy; Neoplasms, Second Primary - etiology; Prednisone - administration & dosage; Quality of Life; Thalidomide - administration & dosage; Thalidomide - adverse effects; Thalidomide - analogs & derivatives
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2014-12-613927

This phase 3 trial (Eastern Cooperative Oncology Group [ECOG] E1A06) compared melphalan, prednisone, and thalidomide (MPT-T) with melphalan, prednisone, and lenalidomide (mPR-R) in patients with untreated multiple myeloma (MM). A noninferiority design was used, and inferiority was defined as a progression-free survival (PFS) hazard ratio (HR) of MPT-T/mPR-R ≤0.82. A total of 306 patients enrolled, with a median age of 75.7 years. Median follow-up was 40.7 months. Median time on therapy was 12.1 months and 23.1 months for the 46.6% of treated patients who received maintenance, with no differences by arm. Median PFS was 21 months on MPT-T and 18.7 months on mPR-R (HR, 0.84; 95% confidence interval, 0.64-1.09). Overall survival was 52.6 months (MPT-T) vs 47.7 months (mPR-R) (P = .476). Per-protocol response rates were 63.6% (MPT-T) and 59.9% (mPR-R) (P = .557). Grade ≥3 nonhematologic toxicity was 59.5% for MPT-T vs 40.0% for mPR-R (P = .001). Second malignancies were observed in 18 MPT-T patients vs 14 mPR-R patients. Quality-of-life analysis favored mPR-R by induction end (P = .007). Use of MPT-T or mPR-R in elderly patients with untreated MM demonstrates no statistical or clinically relevant differences in response rates, PFS, and OS; however, quality of life at end of induction was improved and lower toxicity reported with mPR-R. This trial was registered at www.clinicaltrials.gov as #NCT00602641. •In a randomized phase 3 trial, overall response rates, PFS, and overall survival were similar between MPT-T and mPR-R.•Toxicity with both regimens was common, but mPR-R was better tolerated, and patients on the mPR-R regimen reported better quality of life.